Mitochondria and cancer

Dysfunction, immunity and emerging therapeutic strategies

Abstract

This study presents an integrative narrative review on the role of mitochondria in oncogenesis, highlighting their involvement in energy metabolism, cellular signaling, immune modulation, and metastasis, as well as the therapeutic implications of these processes. A literature search was conducted in PubMed, ScienceDirect, Nature Portfolio, SpringerLink, and PubMed Central, including articles published between 2020 and 2025. The review covered studies on tumor mitochondrial metabolism, mitochondrial DNA alterations, retrograde signaling, tumor microenvironment interactions, and mitochondria-targeted therapies. Findings indicate that mitochondrial dysfunction occurs at multiple stages of tumor progression, conferring metabolic plasticity, therapy resistance, and immune evasion capacity. Recent evidence supports the “mitochondria-first” hypothesis, suggesting that primary organelle alterations may precede nuclear mutations in certain cancers. Emerging therapeutic strategies include oxidative phosphorylation inhibitors, mitochondrial membrane permeability modulators, and targeted nanotechnologies, many of which show promise when combined with immunotherapy. In conclusion, mitochondria represent strategic targets for novel oncological approaches; however, robust clinical studies are still required for validation and safe implementation of such therapies.